Diagnosis of Pheochromocytoma

Verified August 17, 2017 by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Sponsor:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

ClinicalTrials.gov Identifier:

NCT00004847

First Posted: March 3, 2000

Last Update Posted: September 13, 2017

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The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth.

Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following:

Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out.

Further study details as provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Primary Outcome Measures:

To investigate the use of radiopharmaceutical tracer, F(18)-FLT for PET/CT scan in evaluating cellular proliferative behavior of various genetically inherited and sporadic pheochromocytomas and paragagliomas in adult patients.

Estimated Enrollment:

2400

Study Start Date:

February 29, 2000

Detailed Description:

Pheochromocytomas and paragangliomas are rare but clinically important chromaffin cell tumors that typically arise from the adrenal gland or from extra-adrenal paraganglia, respectively and constitute a surgically correctable cause of chronic hypertension. The clinical features and consequences of pheochromocytoma/paraganglioma result from the release of catecholamines (e.g., norepinephrine and epinephrine) by the tumor. If a pheochromocytoma/paraganglioma is undetected, stimuli that normally would not pose a hazard, such as surgery, childbirth, or general anesthesia, can evoke catecholamine secretion by the tumor, with clinically significant and even catastrophic outcomes. The diagnosis of pheochromocytoma/paraganglioma and its localization can be challenging, because measurements of plasma levels or urinary excretion of catecholamines and their metabolites as well as radio-iodinated metaiodobenzylguanidine (MIBG) scanning can yield false-positive/negative results in patients harboring the tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to the development of pheochromocytoma/paraganglioma remain unknown, even in patients with identified mutations. Moreover, pheochromocytomas/paragangliomas in patients with hereditary predispositions differ in terms of their growth, malignant potential, catecholamine phenotype, responses to standard screening tests, such as the clonidine suppression test, various imaging modalities, and different therapeutic options. This protocol focuses on developmental, molecular, genetic, epigenetic, proteomic, metabolomics, and other types of studies to elucidate the bases for predisposition to develop pheochromocytomas/paragangliomas and for expression of different neurochemical phenotypes and malignant potentials including therapeutic responses. Furthermore, this protocol will also use new imaging approaches, for example [(18)F]-6F-dopamine ([(18)F]-6F-DA), [(18)F]-L-3,4-dihydroxyphenylalanine ([(18F)]-DOPA), and [(68)Ga]-DOTA-Tyr-octreotate ([(68)Ga]-DOTATATE) positron emission tomography (PET)/CT, as well as PET/MRI scanning, and dynamic contrast-enhanced MRI. Additionally, new biochemical diagnostic criteria exist for the measurement of plasma metanephrines and methoxytyramine for the clinical diagnosis and localization of these tumors. This protocol will also evaluate the benefits of histone deacetylase inhibitors (e.g. romidepsin) pretreatment for uptake enhancement of [(123/131)I]-MIBG in pheochromocytoma/paraganglioma tumors.

Eligibility

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Ages Eligible for Study:

7 Years and older (Child, Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

INCLUSION CRITERIA:

Patients are adults or children of any age with known or suspected sporadic or familial pheochromocytoma/paraganglioma, on the basis of one or more of the following:

High levels of blood or urinary catecholamines, metanephrines, methoxytyramine, or chromogranin A.

Highly suspected presence of pheochromocytoma or paraganglioma based on imaging studies, even with normal biochemistry.

Personal or family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop pheochromocytoma/paraganglioma.

Normal volunteers over the age of 18 years old, including those with normal or high blood pressure, are to be used for reference values regarding biochemical and imaging diagnosis of pheochromocytoma and paraganglioma.

Patients and normal volunteers can be studied to provide blood/urine samples for biochemical, proteomic, and/or genetic and epigenetic analysis.

Signed informed consent is required.

Patients must be willing to return to NIH for follow-up evaluation.

Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.

Patients with pheochromocytoma/paraganglioma will be accepted through clinician or self- referrals.

EXCLUSION CRITERIA:

Potential patients will be excluded on the basis of one or more of the following;

Pregnant or breastfeeding women

Severe cardiac dysfunction

Currently on dialysis

If a previously enrolled female becomes pregnant, no imaging studies or biochemical workup will be performed until after delivery or the conclusion of breastfeeding. A pregnancy test is performed in women of childbearing age (up to age 55). In those with a positive pregnancy test, no PET and MIBG scanning contrast CT, DCE-MRI vena cava sampling or the clonidine test are performed.

Research scans are contraindicated in patients with myelodysplastic syndrome.

Patients who are not willing to return to the NIH (e.g., after surgery or an initial evaluation) for more than 2 years may be removed from the protocol.

Patients with a body weight of (Bullet)400 pounds due to weight limitations of PET/CT/MRI scanners or patients who are not able to enter the bore of PET/CT/MRI scanners due to BMI,

Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.),

---Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.),

---Any additional medical conditions, serious illness, or other extenuating circumstance that, in the opinion of the Principal Investigator, may significantly interfere with study compliance.

---Additionally, DCE-MRI is not done in patients with acute or chronic renal insufficiency since gadolinium chelate injection is contraindicated in those patients. In patients where DCE-MRI is considered, a creatinine clearance measurement is performed as a clinically indicated test by the Department of Laboratory Medicine at the NIH Clinical Center. Patients with impaired kidney function will not undergo DCE-MRI. DCE-MRI is also not done in patients with severe claustrophobia or who have iron or metal in the MRI scan site, in patients with pacemakers or defibrillators, or in patients with an allergy to gadolinium.

-In pediatric patients:

--Inclusion criteria for research PET imaging in children

---Children over 10 years old with very high suspicion of sporadic or familial pheochromocytoma/paraganglioma (e.g. the presence of new onset of hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.) family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop these tumors, or the presence of a tumor on conventional imaging /ultrasounds, CT, MRI.

Children must give written informed assent and be willing to return to the NIH for follow-up.

Female patients of childbearing age must have a negative pregnancy test within 24 hours of any treatment or test involving radioactivity or radiation exposure. They should be abstinent or use appropriate contraception while in the part of the study, which involves radiation.

--Exclusion criteria for research PET imaging in children

Children of less than 10 years of age,

Children with impaired mental capacity that precludes informed assent,

Pregnant or lactating female adolescents,

Inability to lie still for the entire imaging time (e.g. cough, turbulent children, severe claustrophobia, etc.).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004847